DNA methylation age is associated with mortality in a longitudinal Danish twin study.

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Abstract

An epigenetic profile defining the DNA methylation age (DNAm age) of an individual
has been suggested to be a biomarker of aging, and thus possibly providing a tool
for assessment of health and mortality. In this study, we estimated the DNAm age of
378 Danish twins, age 30-82 years, and furthermore included a 10-year longitudinal
study of the 86 oldest-old twins (mean age of 86.1 at follow-up), which subsequently
were followed for mortality for 8 years. We found that the DNAm age is highly correlated
with chronological age across all age groups (r = 0.97), but that the rate of change
of DNAm age decreases with age. The results may in part be explained by selective
mortality of those with a high DNAm age. This hypothesis was supported by a classical
survival analysis showing a 35% (4-77%) increased mortality risk for each 5-year increase
in the DNAm age vs. chronological age. Furthermore, the intrapair twin analysis revealed
a more-than-double mortality risk for the DNAm oldest twin compared to the co-twin
and a 'dose-response pattern' with the odds of dying first increasing 3.2 (1.05-10.1)
times per 5-year DNAm age difference within twin pairs, thus showing a stronger association
of DNAm age with mortality in the oldest-old when controlling for familial factors.
In conclusion, our results support that DNAm age qualifies as a biomarker of aging.